DESCRIPTION: (Applicant's Abstract) The analysis of hair for drugs of abuse is the most rapidly growing area in drug detection. It also has the potential to be used to determine compliance or recidivism in drug-abuse treatment programs, to provide a scientific marker for epidemiological studies of drug abuse, to serve as a deterrent to drug usage by fear of detection, and to aid in the detection of potential drug exposure in fetuses by drug detection in the mother during pregnancy and in the newborn at birth. Drugs can be detected in hair at times when the plasma or urine does not contain measurable concentrations of drugs. During the previous grant period we have developed analytical methods to measure codeine, morphine cannabinoids, phenobarbital, MDMA, and methamphetamine in hair. We have also determined that codeine is incorporated into animal and human hair in a dose-proportional manner; that codeine and morphine, but not phenobarbital, are preferentially incorporated into black hair versus white hair; that there are specific binding sites for codeine and morphine in black, but not white, hair; that human hair grafted onto athymic mice will serve as a model for the incorporation of drugs of abuse; and that codeine can be detected in human hair within 30 minutes after a single dose, and continue to be detected in hair for at least 10 weeks. In this continuation, we will expand on these findings and develop new methods to study drug incorporation into hair. Specifically, we will, 1) develop analytical methods for measuring the unique metabolites of drugs of abuse in hair using LC/MSMS; 2) localize the distribution of drug binding in hair components using immunohistochemistry with electron microscopy visualization; 3) determine the relationship between the hair melanin concentration and drug incorporation into hair; 4) characterize the incorporation of PCP into hair and study its binding to isolated melanosomes; 5) determine the role of gender and hair color in drug incorporation into the hair of human subjects; and 6) determine, in human subjects, whether actively dividing hair-forming cells are required for drug incorporation. Experiments to achieve these aims will provide data for the careful scientific study of the factors controlling the disposition of drugs of abuse in human hair.